ATYPICALS ANTIPSYCHOTIC MEDICATIONS

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1 The atypical antipsychotics are a class of drugs that are used to treat a number of behavioral health disorders, including schizophrenia, other psychotic disorders, mood disorders, and behavioral agitation in children with autism. There is also some off label uses which include the treatment of agitation in dementia and sleep disturbances seen in a variety of mental health disorders. This class of medications offers several treatment advantages, but they are not without risk. As always, a risk-benefit analysis should be done with your patients to determine the most clinically appropriate course of action. The information, which follows, provides a brief overview of the atypicals and factors to consider when determining the most appropriate treatment for your patients. It is not meant to be fully inclusive, and supporting information should be utilized if necessary. There are currently 10 different atypical antipsychotics on the market. Many of the atypicals now have a generic equivalent. Four of the atypicals have a long acting injection as well. None of the second generation long acting agents have a generic equivalent. All of the atypicals target the blockade of D2 receptors. An additional range of binding activity at other receptor sites may account for different adverse effects seen between each medication in this class. The first generation antipsychotic medications are effective but also problematic due to the high incidence of extrapyramidal symptoms and other adverse effects such as hyperprolactinemia. In the CATIE trial (Clinical Antipsychotic Trials of Intervention Effectiveness), it was determined that the atypical medications were not more effective than the typical antipsychotic perphenazine. It should also be noted that the atypicals are not without risk for weight gain, high cholesterol and diabetes. COMPARISON OF ATYPICAL ANTIPSYCHOTICS GENERIC (BRAND)/ COST FDA-APPROVED INDICATIONS AND USUAL OR TARGET ADULT DAILY DOSE METABOLIC WEIGHT GAIN ADVERSE DIABETES RISK EVENTS DYSLIPIDEMIA QT PROLONGATION CYP3A4 METABOLISM SEDATION A,19 Schizophrenia: mg Aripiprazole (Abilifytk,L 10 mg $ Bipolar disorder (acute manic or mixed episodes; maintenance): 15 mg Depression (adjunct): 5-10 mg Low to none None None Yes Yes Low Asenapine (Saphris)m 20mg $ Schizophrenia: 10 mg (acute), 20 mg (maintenance) Bipolar disorder (acute manic or mixed episodes): mg Low to none Low to none Low to none Yes d Yes (minor) Low to Moderate For sublingual use. A void food or 1

2 GENERIC (BRAND)/ COST FDA-APPROVED INDICATIONS AND USUAL OR TARGET ADULT DAILY DOSE drink for 10 min. after administration. METABOLIC WEIGHT GAIN ADVERSE DIABETES RISK EVENTS DYSLIPIDEMIA QT PROLONGATION CYP3A4 METABOLISM SEDATION A,19 Clozapine (Clozaril, generics) 300 mg $ Schizol2hrenia (treatment-resistant): mg Recurrent suicidal behavior risk reduction in schizol2hrenia & schizoaffective disorder: mg High High High Yes Yes High Iloperidone (Fanapt) 12 mg $ Schizol2hrenia: mg Moderate Low Low Yes c Yes Low Lurasidone (Latuda) 40mg $ Schizol2hrenia: mg Take with food. Low Low Low or none No Yes Moderate Schizol2hrenia: mg Olanzapine (Zyprexa, generics ) f,k 10 mg $15.75 Bipolar disorder (acute manic or mixed episodes; maintenance): 5-20 mg Depression (associated with bipolar disorder), with fluoxetine: mg High High High Yes No Moderate Depression (treatment-resistant), with fluoxetine: 5-20 mg Paliperidone (Invega)g 6mg $ Schizol2hrenia: 3-12 mg Schizoaffective disorder (acute): 3-12 mg Low Low None Yes Yes (minor) Low 2

3 GENERIC (BRAND)/ COST FDA-APPROVED INDICATIONS AND USUAL OR TARGET ADULT DAILY DOSE METABOLIC WEIGHT GAIN ADVERSE DIABETES RISK EVENTS DYSLIPIDEMIA QT PROLONGATION CYP3A4 METABOLISM SEDATION A,19 Quetiapine (Seroquel, generics) 400mg $32.46 Schizophrenia: mg Bipolar disorder (acute depression): 300mg Bipolar disorder (acute mania, maintenance [adjunct]): mg Schizophrenia: mg Quetiapine (Seroquel XR) 400mg $ Bipolar disorder (acute depression): 300 mg Bipolar disorder (manic or mixed episodes; maintenance [adjunct]): mg Major depressive disorder [adjunct]: mg Take without food or with a light meal (about 300 kcal). Moderate Moderate Moderate Yes d Yes Moderate Risperidone (Risperdal, generics) h.k,l 4mg $1l.22 Schizophrenia: 4-8 mg Bipolar disorder (acute manic or mixed episodes): 1-6 mg Moderate Moderate Low Yes No Low 3

4 DRUG-DRUG INTERACT IONS INVOLVING ANTIPSYCHOTIC MEDICATIONS Increased psychotic levels Decreased antipsychotic levels Inhibitors of P450 la2,206, 3A4 including fluoxetine, paroxetine, fluvoxamine, nefazodone, bupropion, duloxetine, flouroquinolones and macrolide antibiotics, antifungals Beta-blockers (lipophilic), carbamazepine, Phenobarbital, phenytoin, rifampin Interference with antipsychotic Antacids (aluminum, magnesium) drug absorption Prolonged cardiac conduction Calcium channel blockers, TCAs, inhibitors of P450 isoenzyme activity (cf. above) Hypotension Antihypertensives, MAO Is, TCAs, trazadone, vasodilators Anticholinergic toxicity TCAs, benztropine, diphenydramine, mirtazapine Interference with dopaminergic effects Bromocriptine, L-dopa, pramipexole, ropinirole Additive risk of myelosuppression (clozapine) Carbamazepine, AZT ADVANTAGES OF THE ATYPICAL VERSUS THE TYPICAL ANTIPSYCHOTICS Wider range of indications Improve both positive and negative symptoms of schizophrenia Smaller risk of extrapyramidal symptoms Smaller risk of Tardive dyskinesia DISADVANTAGES OF THE ATYPICAL ANTIPSYCHOTICS VERSUS THE TYPICAL ANTIPSYCHOTICS Cost Increased risk of metabolic syndrome Increased risk of diabetes/hyperglycemia Increased risk of hyperlipidemia 4

5 OTHER FACTORS TO CONSIDER Risperidone, Olanzapine, Quetiapine, Clozapine as well as some of the typicals can cause significant weight gain. Any patient who is placed on an atypical antipsychotic needs to be monitored on the following parameters BMI, fasting blood glucose, cholesterol and triglycerides. Those patients on Geodon should have a baseline EKG, secondary to the risk of QT prolongation. It should be avoided with other medications which can prolong the QT interval. Patients on Seroquel should have baseline and 6 month slit lamp examinations for the development of cataracts. Clozapine increases the risk for seizure as well as the risk for agranulocytosis. Iloperidone should be avoided in those with hepatic impairment. The use of the atypicals in the management of psychosis and agitation in the elderly with dementia is not FDA approved and carries an increased risk of cerebrovascular events. None of the atypicals are FDA approved for the treatment of insomnia. 5

6 Bibliography Sadock, Benjamin and Virginia, Synopsis in Psychiatry, Lippincott Williams & Wilkins ninth edition 2003 Stern, Theodor and Herman, John, Massachusetts General Hospital Psychiatry Update and Board Preparation, McGraw-Hill, second edition Pharmacist s letter/prescriber s Letter, Comparison of Atypical Antipsychotics, October 2012, Older Medication Just as Effective as Newer Medication for Patients with Schizophrenia, Zacher, Jennifer and Holmes, Jamie Second-generation antipsychotics: A review of recently-approved agents and drugs in the pipeline, journal.modernmedicine.com/formulary-journal/news/clinical/clilnical-pharmacists 6

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